Disruption of biomolecule function by nanoparticles: How do gold nanoparticles affect Phase I biotransformation of persistent organic pollutants?

Size- and time-dependent alteration in metabolic activities of human hepatic cytochrome P450 isozymes by gold nanoparticles via microsomal coincubations

“…However, this result was inconsistent with our findings. While a tannic-enzyme interaction makes up some of the CYP inhibitions occurring, there are likely to be many other pristine complicated NP-related interactions during the coincubation in that many CYP reactions could also be inhibited by citrate-capped AuNPs [ 24 , 26 ] or in a size-dependent manner and that CYP1A2 is found to be more undisturbed.…”

“…As for cytochrome P450 enzymes, a variety of irreversible inhibitors proved to be selective mechanism-based inactivators (suicide substrates) through their chemical modifications of the CYP heme and/or heme-thiolate proteins. Recently, most nanosized particles have been reported to inhibit a CYP activity due to direct electrostatic interactions and/or microenvironment changes in the surrounding ionic strength [ 21 - 26 ], while no data on time-dependent inactivation have been reported so far. In our study, tannic acid-decorated AuNPs were demonstrated to inhibit CYP2D6 and CYP3A4 in a time-dependent but NADPH-independent manner, indicating a conformational change in the enzyme during the slow and tight-binding and thereby affecting its biotransformation activity.…”

“…Most recent studies focus on the NP-induced (negative) effects on enzymatic functions, but scarce reports of the potential impact of incubation matrix components on NPs have been published. Owing to the potentially complex interplays between NPs and biomolecules (e.g., corona) and ions (e.g., aggregation) in their environs, the mechanisms behind the disruption of CYPs and other cellular components (e.g., microsome membrane) in general are not necessarily obvious [ 26 ]. In the present study, we aimed to examine not only the effects of AuNPs on activity and kinetics of the five major human CYP450 isoenzymes (1A2, 2C9, 2C19, 2D6, 3A4) using the in vitro microsomal system but also the changes in properties of AuNPs during the incubation period.…”

Biomarkers of susceptibility: State of the art and implications for occupational exposure to engineered nanomaterials

“…In fact, several in vitro studies reported the ability of different metal, metal oxide as well as carbon based and polymeric NPs to acutely (after up to 24 h of treatment) or sub-acutely (after up to 48 h of treatment) affect the gene (Alshatwi et al, 2013; Hitoshi et al, 2012; Periasamy et al, 2014) and mRNA expression (Hitoshi et al, 2012; Lammel et al, 2015) as well as the functionality (Christen and Fent, 2012; Fröhlich et al, 2010; Kulthong et al, 2012; Lu et al, 2013; Lamb et al, 2010; Sereemaspun et al, 2008; Warisnoicharoen et al, 2011; Ye et al, 2014) of CYP metabolic enzymes, although with different results maybe in relation to the type and physico-chemical characteristics of the NPs investigated. Moreover, induction or inhibition of CYP450 gene (Balasubramanian et al, 2010; Ji et al, 2009), mRNA (Cui et al, 2010; Sun et al, 2012) and protein expression (Coccini et al, 2013), as well as alterations in its metabolic functionality (Cho et al, 2010; Kulthong et al, 2012) were also reported in in vivo studies under various conditions of exposure involving a series of different NPs (Table 1).…”

“…The physicochemical properties of NPs may be responsible for driving different types of NP-CYP450 interactions, i.e. directly affecting CYP gene expression changes (Hitoshi et al, 2012) and physical enzyme conformation, thus leading to perturbations in the stereo-selective enzymatic metabolism or indirectly inducing enzymatic micro-environment alterations (Fröhlich et al, 2010; Lamb et al, 2010; Lu et al, 2013; Ye et al, 2014). The hydrophobicity, surface charge, the larger curvature of smaller NPs as well as the surface capping agents at the NP-enzyme interface have all emerged as features potentially affecting NP-enzyme and NP-enzymatic microenvironment interactions in vitro (Ye et al, 2014).…”